In order to have a functional nervous system the processes of neurons must travel accurately over relatively long distances and connect to the appropriate targets during development. Similarly, if these connections are interrupted in adults, function is not restored until the fibers are guided back to establish contact with their target. The long term goals of this project are to understand the molecular basis of axonal guidance in vivo by identifying and characterizing molecules that induce and guide initial outgrowth of axons. This will lwas to a better understanding of how incorrect connections may get made during development, and how they might be corrected; this information will also be useful for designing ways to assist regenerating axons so they once again make functional connections. Outgrowth of axons from the submandibular ganglion will be examined in tissue culture. The neurons will be presented with substrates of different composition to test whether they are capable of stimulating process outgrowth. The neurons will also be grown in the presence of their normal target, the salivary gland epithelium. The epithelium is necessary for inducing nerve outgrowth. In addition nerves grow over the epithelium in a specific pattern. Modifications of the epithelium will be used to examine the nature of molecules necessary for inducing and directing nerve growth. Once sources of neurite outgrowth stimulating activity are identified monoclonal antibodies will be generated. They will be screened for the ability to inhibit neurite outgrowth stimulated by the substrate. Function-blocking antibodies isolated and identified in this study will serve as specific probes for the localization and purification of related molecules in other target organs.